Lung heparan sulfates modulate Kfc during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction
- 1 May 2012
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 302 (9), L816-L828
- https://doi.org/10.1152/ajplung.00080.2011
Abstract
Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient ( Kfc) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in Kfc. Isolated perfused rat lung preparation was used to measure Kfc in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered Kfc in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on Kfc, demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in Kfc. Ventilation strategies altered lung NO concentration and the Kfc response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies.Keywords
This publication has 49 references indexed in Scilit:
- Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injuryAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2011
- Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stressBiomaterials, 2011
- The use of an endothelium-targeted cationic copolymer to enhance the barrier function of lung capillary endothelial monolayersBiomaterials, 2009
- The endothelial glycocalyx mediates shear-induced changes in hydraulic conductivityAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4American Journal of Respiratory Cell and Molecular Biology, 2008
- Fluorescence correlation spectroscopy can probe albumin dynamics inside lung endothelial glycocalyxAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2007
- The role of endothelial glycocalyx components in mechanotransduction of fluid shear stressBiochemical and Biophysical Research Communications, 2007
- The endothelial glycocalyx: composition, functions, and visualizationPflügers Archiv - European Journal of Physiology, 2007
- Comparison of Two Fluid-Management Strategies in Acute Lung InjuryThe New England Journal of Medicine, 2006
- Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress SyndromeThe New England Journal of Medicine, 2000